Recent developments in alcoholism:genetic transmission.

This chapter is an overview of developments in the study of genetic factors in vulnerability in alcoholism. The focus is on recent developments, including heritability studies in twins and transmission studies in families, both of which have continued to reveal evidence for a substantial role for genetic factors but also for etiologic complexity and variation in vulnerability across generations and across cultures. Studies are discussed which utilized psychophysiological and neurochemical markers for alcoholism for analysis of genetic association, transmission, and linkage. These markers include the low P300 event-related potential, sensitivity to ethanol's intoxicating and euphoric effects, platelet adenylate cyclase, and neurotransmitter metabolite concentrations. Although it is highly likely that many alcoholism-associated physiologic phenotypes are secondary traits, these approaches have increased the specificity of genetic analyses and genetic analyses are clarifying their relationship to alcoholism. For example, early efforts to study, in families, the co-occurrence of the P300 marker and alcoholism have yielded results indicating that the P300 abnormality precedes significant exposure to alcohol and that relatives of alcoholics are more likely to have this trait. In the area of animal models, two nonhuman primate species, the vervet monkey and the rhesus macaque, were shown to willingly consume alcohol to intoxicating blood levels. Also, linkage studies using the quantitative trait locus (QTL) mapping strategy were attempted for phenotypes relevant for alcoholism. The QTL strategy is theoretically capable of identifying determinant genes which contribute only a small portion of the variance. In human linkage studies, a genetic association was found to the DRD2 dopamine receptor. The DRD2 finding generated controversy, as a number of other groups failed to replicate it, and also focused attention on the advantages and pitfalls of the population association approach for detecting genes influencing behavior. The relationship of the alcohol metabolic gene variants to alcoholism was clarified by the finding that functional variants of alcohol and aldehyde dehydrogenases can act additively to determine vulnerability to alcoholism.